**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Shinji Masuko, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Japan

**Main Body of the Abstract**
Background: Patisiran is an RNA interference therapeutic approved for ATTRv amyloidosis. Patisiran was shown to halt or inhibit progression of neuropathy and cardiomyopathy, however, little is known about its effect on reduction of amyloid deposition.
Objective: To elucidate the effect of patisiran on reduction of amyloid deposition.
Methods: Amyloid deposition was assessed by gastroduodenal biopsy (N=19) and 11C-Pittsburgh compound B (11C-PiB) PET (N=6) before and after 2 years of patisiran treatment. In the biopsy analysis, % area of amyloid deposition in the gastroduodenal mucosa was quantified by Congo red staining. In the 11C-PiB PET analysis, Myocardium / Background Ratio (MBR) was used, defined as (standardized uptake value (SUV) myocardium / SUV background).
Results: In the biopsy analysis, % area of amyloid deposition in the gastroduodenal mucosa following 2 years of patisiran treatment (1.07 ± 1.28) was significantly lower than that at baseline (4.18 ± 3.70; P= 0.0004, paired t test). Amyloid deposition disappeared in 3 patients. Mean % amyloid reduction with patisiran was 60.2 ± 35.7%. In the 11C-PiB PET analysis, MBR at 2-year follow-up (2.82 ± 0.82) was significantly lower than that at baseline (4.01 ± 1.24; P = 0.007, paired t test). Mean % MBR reduction with patisiran was 28.7 ± 16.7%.
Discussion and Conclusions: Patisiran significantly reduced amyloid deposition in the gastroduodenal mucosa and heart. Our results suggest the existence of an intrinsic ATTR amyloid degradation system in the human body, since a reduction in amyloid deposition was observed by inhibiting production of TTR.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Shinji Masuko, Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Japan

**Main Body of the Abstract**
**Background:** Patisiran is an RNA interference therapeutic approved for ATTRv amyloidosis. Patisiran was shown to halt or inhibit progression of neuropathy and cardiomyopathy, however, little is known about its effect on reduction of amyloid deposition.
**Objective:** To elucidate the effect of patisiran on reduction of amyloid deposition.
**Methods:** Amyloid deposition was assessed by gastroduodenal biopsy (N=19) and ^11^C-Pittsburgh compound B (^11^C-PiB) PET (N=6) before and after 2 years of patisiran treatment. In the biopsy analysis, % area of amyloid deposition in the gastroduodenal mucosa was quantified by Congo red staining. In the 11C-PiB PET analysis, Myocardium / Background Ratio (MBR) was used, defined as (standardized uptake value (SUV) myocardium / SUV background).
**Results:** In the biopsy analysis, % area of amyloid deposition in the gastroduodenal mucosa following 2 years of patisiran treatment (1.07 ± 1.28) was significantly lower than that at baseline (4.18 ± 3.70; _P_= 0.0004, paired t test). Amyloid deposition disappeared in 3 patients. Mean % amyloid reduction with patisiran was 60.2 ± 35.7%. In the ^11^C-PiB PET analysis, MBR at 2-year follow-up (2.82 ± 0.82) was significantly lower than that at baseline (4.01 ± 1.24; _P_ = 0.007, paired t test). Mean % MBR reduction with patisiran was 28.7 ± 16.7%.
**Discussion and Conclusions:** Patisiran significantly reduced amyloid deposition in the gastroduodenal mucosa and heart. Our results suggest the existence of an intrinsic ATTR amyloid degradation system in the human body, since a reduction in amyloid deposition was observed by inhibiting production of TTR.



Reduction of amyloid deposition by patisiran －Evaluation by gastroduodenal biopsy and amyloid 11C-Pittsburgh compound B PET PC117 (#228)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.